Rephaeli Ada, Gil-Ad Irit, Aharoni Ana, Tarasenko Igor, Tarasenko Nataly, Geffen Yona, Halbfinger Efrat, Nisemblat Yotam, Weizman Abraham, Nudelman Abraham
Laboratory of Pharmacology and Experimental Oncology, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.
J Med Chem. 2009 May 14;52(9):3010-7. doi: 10.1021/jm900143u.
The GABA amides of the antidepressants nortriptyline and fluoxetine, 1 and 2, were compared to their respective parent compounds in rodent models of pain. The amides significantly reduced early nociceptive and late inflammatory responses compared to nortriptyline or fluoxetine, where 1 exhibited overall better efficacy than 2. Amide 1 was most efficacious in lowering cytokine secretion, edema and hyperalgesia induced by formalin and lambda-carrageenan, respectively. Thus, 1 is a promising candidate for the treatment of pain.
在啮齿动物疼痛模型中，将抗抑郁药去甲替林和氟西汀的GABA酰胺（1和2）与其各自的母体化合物进行了比较。与去甲替林或氟西汀相比，这些酰胺显著降低了早期伤害性反应和晚期炎症反应，其中1的总体疗效优于2。酰胺1在降低由福尔马林和λ-角叉菜胶分别诱导的细胞因子分泌、水肿和痛觉过敏方面最有效。因此，1是一种有前景的疼痛治疗候选药物。
